The Future is Today
With the AHNTI Conference underway, it’s fascinating to see how many modalities get discussed in the same rooms in a growing field like Animal Health. This is something so incredible, if we just think how much time it took for Human Health to develop these technologies, and a single conference will definitely not be enough to get together experts and decision makers in a meaningful way. This is an incredible moment for Animal Health, in which all these technologies are available, and so much is still to be done. It’s exciting, and it’s just the beginning. Enjoy this week’s newsletter! Davide Confalonieri, PhD | CEO @Lab4Paws In Vitro How Nutrients Affect Dog and Cat Skin Cells Sun et al. from Nourse Centre for Pet Nutrition, Wuhu, China, explored how certain nutrients affect skin cells in dogs and cats. The study found that keratin hydrolysate, egg yolk lecithin, and fish collagen peptide can help skin cells grow and may promote hair regeneration by affecting a specific signaling pathway (Wnt/β-catenin) in the cells. These nutrients increase the levels of β-catenin protein and promote the expression of genes that are important for skin cell proliferation and hair follicle regeneration. While cow bone collagen protein didn’t show any effect, cysteine promoted skin cell growth but not through the same β-catenin pathway. The research suggests that these nutrients could play a role in maintaining healthy skin and hair in pets, though more in vivo studies are needed. Sun, X., Ma, Y., Gao, Y., Li, J., Li, Y., & Lv, L. (2025). Nutrients regulation of skin cells from canines and cats via Wnt/β-catenin signaling pathway. Frontiers in Veterinary Science, 12. https://doi.org/10.3389/fvets.2025.1486201 Enhanced Stem Cells for Drug-Induced Liver Injury In this study Jing et al. from the College of Veterinary Medicine of Northwest A&F University , China, investigated how canine adipose mesenchymal stem cells can be used to treat drug-induced acute liver injury. The liver, responsible for processing most drugs, is often damaged by them due to individual differences, metabolism variations, and misuse. Mesenchymal stem cells (MSCs) offer a potential treatment because they can regenerate and turn into different cell types. However, MSCs struggle to multiply and survive when grown in the lab and are often eliminated by the body’s immune system. To improve MSCs, scientists modified them to produce more GPX3, an antioxidant that protects against damage, and CD47, a protein that helps cells avoid immune attacks. In mice with drug-induced liver injury, these enhanced MSCs survived better, reduced liver inflammation, and lessened oxidative damage, providing greater protection compared to regular MSCs. Jing, Y., Li, B., Aierken, A., Zhang, Z., Han, D., Lin, Z., Gao, J., Tian, H., & Hua, J. (2025). Mesenchymal Stem Cells with Simultaneous Overexpression of GPX3 and CD47 for the Treatment of Drug-Induced Acute Liver Injury. Veterinary Sciences, 12(2), 149. https://doi.org/10.3390/vetsci12020149 Diagnostics & Biomarkers New Score Helps Guide Treatment for Dog Skin Tumors Lorella Maniscalco from the University of Turin, Italy, and colleagues proposed a new way to score hepatoid gland tumors in dogs to better guide treatment decisions. These tumors are common skin tumors in dogs, but it’s not always clear how they will behave. The researchers developed a scoring system based on what the tumor looks like under a microscope to predict whether the tumor will recur or spread. While a previous marker, Ki67, wasn’t helpful in predicting prognosis in this study, the new scoring system could differentiate tumors with favorable and worse prognoses. The scoring system can help veterinarians make more accurate diagnoses and treatment plans for dogs with these tumors Maniscalco, L., Olimpo, M., Parisi, L., Buracco, P., Mazzone, E., Martinelli, G., Martano, M., Iussich, S., & Morello, E. (2025). A novel scoring system proposal to guide treatment of dogs with hepatoid gland tumors. Frontiers in Veterinary Science, 12. https://doi.org/10.3389/fvets.2025.1451510 PTH Levels in Dogs with Acute Kidney Injury This study by Zambarbieri et al. from the Department of Veterinary Medicine and Animal Sciences, Università degli Studi di Milano , Italy, investigated parathyroid hormone (PTH) levels in dogs with acute kidney injury (AKI) and compared them to dogs with chronic kidney disease (CKD) and healthy dogs. The researchers found that PTH levels were significantly higher in both AKI and CKD groups compared to healthy dogs, but there was no significant difference in PTH levels between the AKI and CKD groups. In dogs with AKI, high PTH levels correlated with the severity of AKI as well as creatinine and phosphate concentrations. PTH was not related to total calcium but was negatively correlated with ionized calcium in AKI dogs. The study suggests that high PTH levels occur in canine AKI, similar to canine CKD and human AKI, likely due to low ionized calcium and high phosphate levels. PTH doesn’t appear to be a useful marker to differentiate between AKI and CKD in dogs. Zambarbieri, J., Monari, E., Dondi, F., Moretti, P., Giordano, A., & Scarpa, P. (2025). Parathyroid Hormone Concentration in Dogs Affected by Acute Kidney Injury Compared with Healthy and Chronic Kidney Disease. Veterinary Sciences, 12(2), 131. https://doi.org/10.3390/vetsci12020131 Clinical Combined Drugs Help Control Eczema in Dogs This study by Ferreira et al. from the Department of Veterinary Medicine, School of Medicine and Life Sciences, Pontifícia Universidade Católica do Paraná ,Brazil, looked at using oclacitinib (Apoquel) and prednisolone (a steroid) to treat itchy skin and inflammation from atopic dermatitis in dogs. One group of dogs received prednisolone first, then a combination of oclacitinib and prednisolone. The other group received oclacitinib alone. Both treatments significantly reduced itching and skin inflammation. The combined treatment was also cheaper than using oclacitinib alone. Ferreira, T. S., Villalobos, W. R., Gmyterco, V. C., Fonseca, D. S., & De Farias, M. R. (2025). Evaluation of oclacitinib maleate and prednisolone combined therapy for the control of atopic dermatitis in dogs: A controlled clinical trial. Veterinary Dermatology. https://doi.org/10.1111/vde.13327 Stem Cell Eye Drops Help Heal Dog Eye Ulcers A study by Casado-Santos et al. from Department of Surgery, Medicine and Veterinary Anatomy, of the Universidad de León ,Spain found that eye drops made from mesenchymal stem cell secretome (substances secreted by stem cells) can effectively heal stubborn corneal ulcers in dogs. The eye drops helped the ulcers heal completely within a few weeks, even when other treatments had failed. The treatment also quickly reduced
We’re Back!
For those of you who are following this newsletter, it should have been easy to see that we skipped the month of January entirely. In the few months from its start, we reached a small audience of people that are interested in weekly updates in Veterinary research, but we had to stand back and look carefully at what we achieved and where we want to take this journey. We feel that there is much to say in Veterinary Science, a budding, growing field with still many missing tools, but we haven’t reached the sweet spot yet where we are able to deliver the max value to our audience. And for this, we need you! What would you like to read? Which news or articles would help you in your work? Let us know as a comment on this newsletter or feel free to send us an email to info@lab4paws.com ! Stay tuned and enjoy this week’s newsletter! Davide Confalonieri, PhD | CEO @Lab4Paws Reviews Guidelines for Treating Canine Transmissible Venereal Tumors: A Review and Analysis Pimentel et al from the Universidade Federal de Minas Gerais , Brazil, conducted a systematic review and meta-analysis to create clinical guidelines for treating canine transmissible venereal tumors (TVT). The study focused on evaluating different treatment options for TVT, which is a type of cancer that can spread between dogs. The authors found that chemotherapy with a drug called vincristine is the most effective first-line treatment. Vincristine is usually given as an injection once a week, and most dogs respond well to this treatment, often achieving complete remission within a few weeks. The review also discussed other treatment methods, such as surgery and radiation therapy, but emphasized that vincristine is the preferred choice due to its effectiveness. The authors highlighted the importance of early diagnosis and treatment to improve outcomes for affected dogs. Overall, the guidelines aim to help veterinarians provide better care for dogs with transmissible venereal tumors by summarizing the best available evidence on treatment options. Pimentel, P. A. B., Giuliano, A., Odatzoglou, P., Ignatenko, N., Wenceslau, R. R., Almeida, I. O., da Silva, P. H. S., Costa, M. P.; Horta, R. D. S. (2025). Clinical Guidelines for Canine Transmissible Venereal Tumour Treatment: Systematic Review and Meta-Analysis. Veterinary and comparative oncology, 10.1111/vco.13038. Advance online publication. https://doi.org/10.1111/vco.13038 SGLT2 Inhibitors for Treating Diabetes in Cats Cook et al. from the Texas A&M College of Veterinary Medicine & Biomedical Sciences , USA, explored the use of SGLT2 inhibitors in managing diabetes in cats. The paper discusses two specific drugs, bexagliflozin and velagliflozin, which have recently been approved for treating feline diabetes. These medications work by helping the kidneys remove excess glucose from the blood, leading to lower blood sugar levels. They are particularly effective for newly diagnosed diabetic cats that still produce some insulin on their own. The study highlights that these drugs can quickly improve blood sugar control and reduce symptoms of diabetes, such as increased thirst and urination. However, they should only be used in cats that have not been previously treated with insulin, as those cats may face serious complications like diabetic ketoacidosis. Overall, the findings suggest that SGLT2 inhibitors offer a promising new option for managing feline diabetes, but careful patient selection and monitoring are essential to ensure safety and effectiveness. Cook, A. K., & Behrend, E. (2025). SGLT2 inhibitor use in the management of feline diabetes mellitus. Journal of veterinary pharmacology and therapeutics, 48 Suppl 1(Suppl 1), 19–30. https://doi.org/10.1111/jvp.13466 How Diet Affects Gallbladder Health in Dogs: A Review In this publication, Fabio Alves Teixeira and co-authors from the School of Veterinary Medicine and Animal Science – São Paulo State University, UNESP , Brazil, reviewed how diet and nutrition can affect gallbladder health in dogs. The paper highlights that certain dietary components, such as fats and fiber, may influence the development of gallbladder diseases. The authors discuss different types of diets and their potential impacts on canine gallbladder function. They also emphasize the importance of understanding these nutritional factors to help prevent and manage gallbladder issues in dogs effectively. Overall, the review aims to provide insights into how proper nutrition can support canine health, particularly regarding gallbladder diseases. Teixeira, F. A., Aicher, K. M.; Duarte, R. (2025). Nutritional Factors Related to Canine Gallbladder Diseases—A Scoping Review. Veterinary Sciences, 12(1), 5. https://doi.org/10.3390/vetsci12010005 SGLT2 Inhibitors: Can They Help Non-Diabetic Pets with Heart and Kidney Problems? Elliott et al. from the Royal Veterinary College ,UK, examined whether sodium glucose transporter 2 (SGLT2) inhibitors could help non-diabetic pets with heart and kidney diseases. The paper highlights that SGLT2 inhibitors are commonly used in humans to manage diabetes and have shown benefits beyond just lowering blood sugar. They can also protect the heart and kidneys, even in people without diabetes. The authors discuss the possibility of using these drugs in dogs and cats with heart or kidney problems, suggesting that they might improve health outcomes for these animals. The study reviews how SGLT2 inhibitors work and their potential protective effects on the heart and kidneys. However, the authors note that more research is needed to fully understand which non-diabetic pets might benefit the most from these medications. Overall, the paper raises interesting questions about the broader use of SGLT2 inhibitors in veterinary medicine and encourages further investigation into their potential benefits for non-diabetic animals with specific health issues. Elliott, J., ; Oyama, M. A. (2025). Sodium glucose transporter 2 inhibitors: Will these drugs benefit non-diabetic veterinary patients with cardiac and kidney diseases?. Journal of veterinary pharmacology and therapeutics, 48 Suppl 1(Suppl 1), 1–18. https://doi.org/10.1111/jvp.13472 Diagnostics & Biomarkers How Decorin, E-Cadherin, and EGFR Levels Affect Outcomes in Dog Mammary Tumors In this article, Bethânia Almeida Gouveia from the Laboratory of USP – Universidade de São Paulo , Brazil, and her colleagues conducted a study on the prognostic implications of specific proteins—decorin, E-cadherin, and EGFR—in canine mammary tumors, both inflammatory and non-inflammatory. The research found that the expression levels of these proteins can provide important information about the likely outcomes for dogs with mammary cancer. Specifically: 1 Decorin: Lower levels of this protein were associated with worse prognosis.
Multimodal diagnosis – but why?
With AI taking over the world, “Multimodal” has become part of our vocabulary. So why not multimodal diagnosis? This week we have two interesting stories of 1H nuclear magnetic resonance (NMR) spectroscopy used to compare serum metabolites and of MRI and immunohistochemistry used in combination to diagnose polymyositis. Now, many of the techniques are used in combination, but actually one after the other. Imagine a world, in which all the techniques can be instantaneously combined and the data integrated. In which IHC stainings can be assembled in 3D to reconstruct the MRI picture and in which metabolites could be traced on the IHCs. All at once. How would this change our understanding of diseases, and times and costs of diagnosis? Enjoy this week’s newsletter! Davide Confalonieri, PhD | CEO @Lab4Paws Reviews The Renin-Angiotensin-Aldosterone System in Cat and Dog Kidney Diseases In this review, Huang et al from the Department of Small Animal Medicine and Surgery, University of Georgia College of Veterinary Medicine, USA explains how the renin-angiotensin-aldosterone system (RAAS) plays a key role in kidney diseases and is a major target of treatment in humans, cats, and dogs. Studies on RAAS in animals with kidney diseases show variable activation and significant individual differences in circulating RAAS markers. Recent discoveries include an “alternative” RAAS and tissue-specific renin-angiotensin systems, such as the intrarenal RAS, which independently regulates kidney function and contributes to kidney disease. Limited data suggest intrarenal RAS activation in cats and dogs with kidney diseases. Despite inconsistent evidence of circulating RAAS activation in chronic kidney disease, RAAS inhibitors effectively treat hypertension and proteinuria in affected cats and dogs. Further research into the circulating and intrarenal RAAS could improve treatment strategies for companion animals with kidney diseases. Jane HC Huang, Bianca N Lourenço, Amanda E Coleman. The Renin-Angiotensin-Aldosterone System in Kidney Diseases of Cats and Dogs. The Veterinary Journal, 2024, 106287, ISSN 1090-0233, https://doi.org/10.1016/j.tvjl.2024.106287. Clinical Localised Apolipoprotein A-I Amyloidosis in a Dog’s Fibroadnexal Hamartoma In this study by Murakami et al. from the Laboratory of Veterinary Toxicology at Tokyo University of Agriculture and Technology in Japan, a rare case of canine apolipoprotein A-I (ApoA-I) amyloidosis is reported. While this condition is typically associated with aging and pulmonary vascular issues, the authors found it in a cutaneous fibroadnexal hamartoma in a dog. Through proteomic analysis using mass spectrometry, the mechanism of ApoA-I amyloidogenesis is explored. Murakami T, et al. (2024). Localised apolipoprotein A-I amyloidosis arising in a fibroadnexal hamartoma in a dog. Veterinary dermatology, 2024(12), Unknown Pages. https://doi.org/10.1111/vde.13316 Successful Diagnosis and Treatment of Canine Polymyositis In this study, Han and colleagues from the Department of Veterinary Internal Medicine at 전남대학교 in Korea report on a case of immune-mediated polymyositis in a dog. The condition was successfully diagnosed using MRI and immunohistochemistry, and effectively managed with immunosuppressive therapy. This highlights the importance of utilizing these techniques for accurate detection and treatment of canine polymyositis. Han J, Park S, Lee K, et al. Successful diagnosis and treatment of canine polymyositis: utilizing MRI and immunohistochemistry for accurate detection. BMC veterinary research. 2024;12:560. https://doi.org/10.1186/s12917-024-04356-6 Topical Dexamethasone Slows Epithelial Movement on the Canine Eardrum Epithelial migration (EM) is crucial for ear health. While glucocorticoids are common treatments for ear issues, their impact on EM in the eardrum and ear canal is not well studied. This study from Kim et al. from the Department of Veterinary Internal Medicine, College of Veterinary Medicine, 경북대학교(Kyungpook National University) , Korea, examined whether topical dexamethasone slows EM on the eardrums of healthy dogs. Seven ears from four dogs were analyzed by measuring the movement of an ink mark on the eardrum over three weeks. Results showed that topical dexamethasone reduced EM rate by nearly 47% compared to untreated controls. This suggests that dexamethasone may slow debris clearance from the ear canal, indicating that additional cleaning might be necessary during treatment for ear conditions. Kim J, Oh T, Bae S. Topical dexamethasone decelerates epithelial migration on the canine tympanic membrane. Vet Dermatol. 2024 Dec 9. https://doi.10.1111/vde.13314 1H NMR Serum Metabolic Profiling in Canine Multicentric Lymphoma Canine lymphoma includes diverse cancers originating from lymphoid cells. Accurate diagnosis is vital for survival outcomes, but current methods are often invasive and lack precision. Metabolomic analysis offers a non-invasive approach to identify biomarkers for diagnosis, treatment response, and prognosis. This study from Solé et al. from the Departamento de Clínicas y Hospital Veterinario, Universidad de la República in Uruguay used 1H nuclear magnetic resonance (NMR) spectroscopy to compare serum metabolites in 37 dogs with multicentric lymphoma (22 B-cell, 9 CD45+ T-cell, and 6 CD45- T-cell lymphomas) and 25 healthy controls. NMR profiling identified lipids and 22 metabolites, with 16 showing significant alterations. Principal component analysis effectively distinguished lymphoma samples from healthy controls. Pairwise comparisons revealed metabolomic similarities across lymphoma immunophenotypes, but five metabolites, including glucose, lactate, N-acetyl glycoproteins, scyllo-inositol, and choline, showed significant differences. These findings suggest changes in energy, protein, and lipid metabolism and highlight potential new biomarkers for canine multicentric lymphoma. Solé RS, Radcenco AL, Moyna G, Breijo M, Pessina P. Application of 1H NMR Metabolic Profiling of Serum in Canine Multicentric Lymphoma. Vet Comp Oncol. 2024 Dec 8. https://doi.10.1111/vco.13034
We are Killing our Pets
Strange but true: we are killing our pets. Slowly, without noticing it. It’s not even big news in the newspapers, but it’s something everyone would be horrified to realize. Pets are getting “humanized” and adapting to the modern society’s lifestyle. And with this, they are getting all the consequences of it, starting from the epidemics and diseases that plague humans, from overweight to cancer. In our work we get to collaborate with many veterinarians from different geographies, and it’s evident that in the most polluted areas, pets are suffering from tumor and immunological disorders more than in others. This raises a question: Are medicaments the only solution or should we approach animal health from a completely different perspective? Enjoy this week’s edition! Davide Confalonieri, PhD | CEO @Lab4Paws Interleukin-6 promotes metastasis in canine oral squamous cell carcinoma cells In this study by Noguchi et al. from the Laboratory of Veterinary Radiology at Osaka Metropolitan University , Japan, it was found that the involvement of interleukin-6 (IL-6) in cancer progression in canine oral squamous cell carcinoma (CoSCC) is not well understood. The researchers aimed to determine the role of IL-6 in CoSCC metastasis by analyzing mRNA and protein expression, as well as cell migration and invasion. Their findings showed that IL-6 levels were elevated in CoSCC tissues and were associated with shorter survival time in dogs. Treatment with recombinant canine IL-6 (rcIL-6) promoted cell migration and invasion, as well as increased expression of certain proteins associated with cancer progression. This study suggests that IL-6 may play a role in the metastasis of CoSCC through specific signaling pathways. Noguchi, S., et al. (2024). Interleukin-6 promotes the epithelial mesenchymal transition in canine tonsillar squamous cell carcinoma cells. Research in veterinary science, 2024(12), 105487. https://doi.org/10.1016/j.rvsc.2024.105487 Do Pre-Treatment Biopsy Characteristics Predict Early Tumour Progression in Feline Diffuse Large B Cell Nasal Lymphoma Treated With RT? In this study from Poirier et al, from the Department of Clinical Studies at Ontario Veterinary College, University of Guelph , Canada, it is shown that pre-treatment biopsy characteristics are not able to predict early tumour progression in feline diffuse large B cell nasal lymphoma treated with radiation therapy. The study evaluated various histologic parameters and found no significant associations with progression-free survival at one year. This suggests that in a uniformly treated population, pre-RT biopsy characteristics may not be reliable predictors of treatment failure. VJ Poirier et al. (2024). Do Pre-Treatment Biopsy Characteristics Predict Early Tumour Progression in Feline Diffuse Large B Cell Nasal Lymphoma Treated With Radiotherapy?. Veterinary and comparative oncology, 2024(12), Unknown Pages. https://doi.org/10.1111/vco.13032 High Prevalence of Overweight and Obese Condition in Dogs and Cats Across Different Life Stages in the USA In this study from Montoya a et al, from Royal Canin anin in France, it is shown that adult dogs and cats are commonly affected by overweight and obese conditions, but there is limited data on prevalence in different life stages, particularly during growth. Using electronic medical records from Banfield Pet Hospital in the USA, the team found that overweight and obese conditions were prevalent in ∼4.9 million dogs and ∼1.3 million cats between 2020 and 2023. These conditions were most prevalent during the mature life stage, and in cases where an animal was overweight or obese during growth, it often persisted into adulthood. The team recommends preventative measures, such as the use of growth standard charts, from an early age to combat this high prevalence of overweight and obese conditions in adult dogs and cats. M Montoya et al. (2024). Overweight and obese body condition in ∼4.9 million dogs and ∼1.3 million cats seen at primary practices across the USA: Prevalences by life stage from early growth to senior.. Preventive veterinary medicine, 2024(12), 106398. https://doi.org/10.1016/j.prevetmed.2024.106398 Multiplexed Immunoassay for Canine Mammary Tumors In this study by Wu et al. from the Graduate Institute of Biomedical Sciences, College of Medicine, 長庚大學 , Taiwan, a multiplexed immunoassay is developed for a serum autoantibody biomarker panel to aid in the diagnostic and prognostic prediction of canine mammary tumors. The results of this study were published in The Veterinary Quarterly in 2024. CC Wu et al. (2024). Multiplexed immunoassay for a serum autoantibody biomarker panel in diagnostic and prognostic prediction of canine mammary tumors. The veterinary quarterly, 2024(12), 1. https://doi.org/10.1080/01652176.2024.2435978
Kidney Health Starts from the Bones
Chronic Kidney Disease (CKD) is a debilitating disease for cats, leading to severe consequences on the animal health. Moreover, it takes also a toll on the mental fitness of owners, who often feel shocked and unprepared to deal with the condition. A large body of research has been collected on the topic, and in this week’s edition Jonathan Elliot and colleagues bring to the point the role of FGF23, a growth factor produced by Osteocytes. This underlines once again the role that studying and modelling diseases with a multi-organ approach has in understanding the disease itself. And of course, in finding diagnostic and therapeutic solutions as well. Enjoy this week’s newsletter! Davide Confalonieri, PhD | CEO @Lab4Paws In Vitro Preliminary Study on the Effects of Cannabidiol and Terpenes on Lymphocytes from Atopic and Healthy Dogs The study by Jani and colleagues from the University of Florida , USA, explores how certain compounds derived from cannabis and plants affect immune cells (lymphocytes) in dogs, particularly those with allergies (atopic) compared to healthy dogs. The research aimed to understand how cannabidiol (CBD), cannabidiolic acid (CBDA), and β-caryophyllene influence lymphocytes, which are crucial for the immune response. This is particularly relevant for dogs with atopic dermatitis, a common allergic condition. The study involved taking lymphocytes from both atopic and healthy dogs and exposing them to different concentrations of CBD, CBDA, and β-caryophyllene in a controlled laboratory setting (in vitro). Researchers then measured the effects on cell activity and function. The results indicated that these compounds could modulate the activity of lymphocytes. Specifically, they showed potential anti-inflammatory effects, which might help in managing allergic reactions in dogs. The compounds appeared to influence how immune cells respond to allergens, which is beneficial for atopic dogs. This preliminary study suggests that CBD, CBDA, and β- caryophyllene may have therapeutic potential for treating allergic conditions in dogs by affecting immune cell behavior. However, further research is needed to confirm these findings and explore their practical applications in veterinary medicine. Jani, T., D. Santoro and J. Shmalberg. Investigation of the in vitro effects of cannabidiol, cannabidiolic acid, and the terpene β-caryophyllene on lymphocytes harvested from atopic and healthy dogs: A preliminary study, Research in Veterinary Science, Volume 182, 2025, 105483, ISSN 0034-5288, https://doi.org/10.1016/j.rvsc.2024.105483. Diagnostics & Biomarkers YKL-40 Levels in Canine Mast Cell Tumors: Prognostic Importance The study by Kuo and colleagues from the 國立臺灣科技大學 , Taiwan, investigates the role of a protein called YKL-40 in predicting the outcomes for dogs with mast cell tumors, which are common skin cancers in dogs. YKL-40 is a protein that is often associated with inflammation and cancer. The study examines how its levels in the blood relate to the severity and progression of mast cell tumors in dogs. Researchers collected blood samples from 82 dogs diagnosed with various types of cancer, including mast cell tumors, and compared their YKL-40 levels to those of 20 healthy dogs. Dogs with cancer had significantly higher levels of YKL-40 compared to healthy dogs. Among dogs with mast cell tumors, those with higher YKL-40 levels were more likely to experience tumor relapse or metastasis (spread of cancer) after treatment. Specifically, dogs with YKL-40 levels above 180 pg/mL had much higher rates of relapse (67.5%) and metastasis (42.5%) than those with lower levels. The study suggests that measuring YKL-40 levels could help veterinarians assess the prognosis for dogs with mast cell tumors. Kuo, CC., Huang, WH., Yang, SY. et al. Prognostic significance of YKL-40 expression in canine cutaneous mast cell tumors. BMC Vet Res 20, 537 (2024). https://doi.org/10.1186/s12917-024-04385-1 Clinical Alopecia Linked to Cancer in a Cat with Apocrine Adenocarcinoma Lupion and colleagues from the Veterinary Hospital in Feevale, Campo Bom, Brazil, investigated a rare case of hair loss (alopecia) in a cat that is believed to be related to an underlying cancer, specifically apocrine gland adenocarcinoma. Apocrine gland adenocarcinoma is a type of cancer that affects the sweat glands and can occur in various locations on a cat’s body, including the anal sac. It is known to be relatively uncommon in cats but can lead to significant health issues. The study details the condition of a specific cat diagnosed with this type of cancer, which exhibited alopecia as a potential paraneoplastic syndrome. Paraneoplastic syndromes are conditions caused by cancer that can affect different body systems, including skin changes. The cat showed notable hair loss, which prompted further investigation into the relationship between the alopecia and the cancer. This case highlights how certain tumors can lead to systemic effects that manifest as skin problems. The findings suggest that alopecia in this cat could be linked to the cancer, emphasizing the need for veterinarians to consider underlying malignancies when presented with unusual skin conditions in pets. Lupion, C. G., Bazotti, M. S., Dos Santos, I. R., Pavarini, S. P., Trindade-Gerardi, A. B., & Gerardi, D. G. (2024). Putative paraneoplastic alopecia in a cat with apocrine adenocarcinoma. Veterinary dermatology, 10.1111/vde.13313. Advance online publication. https://doi.org/10.1111/vde.13313 Review of Fibroblast Growth Factor 23: Its Role in Phosphate Balance in Cats The study by Jonathan Elliot from the Royal Veterinary College , United Kingdom, examines the role of fibroblast growth factor 23 (FGF23) in managing phosphate levels in cats, particularly how it affects their overall health. The study discusses how phosphate homeostasis involves multiple organs, including the kidneys, bones, and intestines. FGF23 works alongside other hormones, such as parathyroid hormone (PTH) and calcitriol (active vitamin D), to control how much phosphate is absorbed from food and how much is excreted by the kidneys. In healthy cats, FGF23 helps prevent excessive phosphate buildup, which can lead to health issues. It signals the kidneys to excrete more phosphate when levels are high and reduces its absorption from the diet. The review also highlights how disruptions in FGF23 levels can contribute to health problems, particularly in conditions like chronic kidney disease (CKD). In CKD, phosphate levels can become elevated, leading to complications such as mineral imbalances and soft tissue calcification. Understanding FGF23’s role is important for managing feline health, especially in older cats or those with kidney issues. Monitoring FGF23 levels
ATR as Cancer Target – It’s coming
ATR as Cancer Target – It’s coming Comparative oncology gives us a lot of insights on how to treat companion animals, and sometimes quite some joy. ATR Kinase inhibitors are not exactly new, the first being developed around 1999, but every new target validated for vet science is a success. And that’s this week’s success from Marta Henklewska et al.! Short recap: ATM, ATR and DNA-PKcs are first responders for DNA repair after DNA damage. While ATM and DNA-PKcs mainly repair double-stranded breaks, ATR repairs single-stranded breaks. So far so good. ATM is quite often mutated, making it one of the most frequently mutated tumor suppressors in cancer. Bad news: the tumor can mutate faster Good news: the tumor is more reliant on ATR for maintaining genomic stability Poor genomic stability -> Apoptosis or Necrosis. Yuppi! This is the concept behind targeting ATR, and what makes this target so promising. With her work, we are a step nearer to validating the target for canine Lymphoma and Leukemia. Enjoy this week’s newsletter! Davide Confalonieri, PhD | CEO @Lab4Paws In Vitro Using ATR Kinase Inhibitors to Treat Canine Lymphoma and Leukemia Marta Henklewska and her team from Wrocław University of Environmental and Life Sciences , Poland, investigated ATR kinase inhibitors as a treatment for canine lymphoma and leukemia. They focused on the drug berzosertib, which targets cancer cells’ ability to repair DNA damage. The study showed berzosertib effectively kills cancer cells without harming healthy cells and works synergistically with the chemotherapy drug chlorambucil. This research suggests ATR inhibition could be a promising new approach for treating these cancers in dogs, though further studies are needed to confirm its potential and identify predictive biomarkers. Henklewska, M., Pawlak, A. and Obmińska-Mrukowicz, B. (2024), Targeting ATR Kinase as a Strategy for Canine Lymphoma and Leukaemia Treatment. Vet Comp Oncol, 22: 602-612. https://doi.org/10.1111/vco.13014 Diagnostics & Biomarkers STAT3 Overactivation in Canine Liver Cancer and Its Impact on Prognosis Shin and colleagues from Seoul National University , South Korea, investigated the role of a protein called phosphorylated STAT3 (pSTAT3) in canine hepatocellular carcinoma (HCC), a type of liver cancer. Their study analyzed tissue samples from healthy dogs, dogs with non-cancerous liver conditions, and dogs with HCC to determine the levels of pSTAT3 and its link to disease progression. The findings revealed that high levels of pSTAT3 were significantly associated with larger tumor sizes, metastasis, and worse survival outcomes. This suggests that pSTAT3 plays a critical role in the aggressiveness of canine HCC. The study highlights its potential as both a marker to predict prognosis and a target for future therapies aimed at improving treatment outcomes for dogs with this condition. Shin, H.K., Chung, H.J. and Kim, W.H. (2024), Overactivation of Signal Transducer and Activator of Transcription 3 in Canine Hepatocellular Carcinoma and Its Prognostic Significance. Vet Comp Oncol, 22: 490-499. https://doi.org/10.1111/vco.12998 Comparing Canine and Human Prostate Cancer to Find Resistance Mechanisms Marcela Riveros Angel gel and colleagues from Oregon Health & Science University , USA, conducted a study to compare gene expression in canine and human prostate cancers, particularly focusing on advanced forms resistant to hormonal treatment, such as castration-resistant prostate cancer (CRPC) in humans and androgen-independent cancers in castrated dogs. Their analysis revealed significant molecular similarities, including shared dysregulated genes like ISG15 and AZGP1, which are linked to immune pathways. These findings suggest that canine prostate cancer could serve as a valuable model to better understand CRPC in humans and potentially guide the development of new therapies targeting shared molecular pathways Angel, M.R., Séguin, B., Löhr, C.V., Beer, T.M., Feliciano, J., Ramsey, S.A. and Thomas, G.V. (2024), Comparative Transcriptomes of Canine and Human Prostate Cancers Identify Mediators of Castration Resistance. Vet Comp Oncol, 22: 629-640. https://doi.org/10.1111/vco.13017 Clinical Testing a New IV Treatment for Canine Lymphoma Using L-Asparaginase Botta and colleagues from the AniCura Animal Oncology and Imaging Center in Switzerland, conducted a pilot study to assess the safety and efficacy of monomeric L-asparaginase administered intravenously in dogs with multicentric lymphoma. This innovative treatment approach aimed to improve outcomes by targeting a critical metabolic vulnerability in lymphoma cells. The study demonstrated that monomeric L-asparaginase could be administered safely, with manageable side effects, and it showed promise in inducing remission in treated dogs. These findings suggest that this approach could complement or enhance existing chemotherapy protocols for canine lymphoma, warranting further research in larger clinical trials to confirm its benefits. Botta, V., Camerino, M., Bicanová, L. et al. Pilot study investigating the intravenous administration of monomeric L-asparaginase to dogs with multicentric lymphoma. Vet. Oncol. 1, 10 (2024). https://doi.org/10.1186/s44356-024-00010-3
Oncolytic Viruses & New Modalities
Oncolytic Viruses & New Modalities This week I had a short exchange on LinkedIn with Brian Krueger, PhD as he was talking about the increasing role of comparative oncology and telling a really personal story on veterinary cancer vaccines (if you missed the post, here the link https://www.linkedin.com/posts/davide-confalonieri-phd_omicly-weekly-50-activity-7264299114249523200-GJoR?utm_source=share&utm_medium=member_desktop ). Quite often we hear about comparative oncology in Vet Science as a way to get inspiration for new therapies, but as Vet research is catching up, I had to ask myself: Is this still the case? After the recent acquisition of Saiba Animal Health AG by Boehringer Ingelheim , bringing Virus-like particles as a new modality in a Big Pharma pipeline, this week we have a great article by Yeganeh Mehrani et al. on the role of Oncolytic Viruses for Mast Cell Tumors. Is the tide going to turn? Enjoy this week’s newsletter! Davide Confalonieri, PhD | CEO @Lab4Paws In Vitro Auranofin Stops Growth and Kills Canine Mammary Tumor Cells by Targeting the PI3K/AKT Pathway This study, by Lin et al. from Fujian Agriculture and Forestry University, Fuzhou, China , focuses on a drug called Auranofin, which has been found to affect the growth of canine mammary tumor cells. The researchers explored how Auranofin works to stop the cancer cells from growing and how it triggers apoptosis, a process where cells are programmed to die. The study specifically looked at how Auranofin affects a key signaling pathway in cells called the PI3K/AKT pathway. This pathway is involved in cell growth, survival, and division. By blocking or altering this pathway, Auranofin helped stop the tumor cells from growing and led them to die off. The research suggests that Auranofin could be a potential treatment for canine mammary tumors by targeting the PI3K/AKT pathway. It opens the door to further studies that may help develop new cancer therapies for dogs with breast cancer. Lin, Z., Chen, R., Wang, J., Zheng, Y., He, Z., Yan, Y., Zhang, L., Huang, X. and Zhang, H. (2024), Auranofin Suppresses the Growth of Canine Mammary Tumour Cells and Induces Apoptosis via the PI3K/AKT Pathway. Vet Comp Oncol, 22: 555-565. https://doi.org/10.1111/vco.13005 Exploring Oncolytic Viruses for Treating Canine Mast Cell Tumors This study by Yeganeh Mehrani et al. from the University of Guelph focuses on mast cell tumors (MCTs), one of the most common types of skin cancer in dogs. While surgery is the primary treatment, some tumors can grow back or spread to other parts of the body, even when they seem less aggressive. The researchers explored the use of oncolytic viruses to treat these tumors. They tested three different viruses on a cell line created from a canine mast cell tumor: Recombinant Vesicular Stomatitis Virus (rVSV-Δm51), Avian Orthoavulavirus-1 (AOaV-1), and Orf Virus. Using advanced laboratory techniques, the team examined how effectively these viruses could infect and kill the tumor cells. Among the three, the rVSV-Δm51 virus showed the strongest ability to destroy cancer cells in lab tests. This study highlights the potential of oncolytic virotherapy as a treatment for canine mast cell tumors, paving the way for further research to determine its effectiveness in real-world clinical settings. The work represents an important step toward developing new, less invasive cancer therapies for dogs. Mehrani, Y., Kakish, J.E., Napoleoni, C., Thompson, J.J., Knapp, J.P., Minott, J.A., Yates, J.G.E., Stuart, D., Coomber, B.L., Foster, R.A., Bridle, B.W. and Karimi, K. (2024), Characterisation and Sensitivity of a Canine Mast Cell Tumour Line to Oncolytic Viruses. Vet Comp Oncol. https://doi.org/10.1111/vco.13024 How Tilmicosin Works Against Mycoplasma synoviae in Labs and Animals This study, led by Yab et al. from Foshan University , China, explores how the antibiotic tilmicosin works to fight Mycoplasma synoviae. The researchers focused on two key aspects: (1) Pharmacokinetics (PK): How the drug moves through the body—how it’s absorbed, distributed, broken down, and eliminated. (2) Pharmacodynamics (PD): How the drug affects the bacteria—how much is needed to stop its growth or kill it. They tested tilmicosin both in the lab (in vitro) and in live animals (in vivo) to understand how it works under different conditions. The goal was to figure out the right dose and treatment approach to make the antibiotic most effective while reducing the risk of resistance. The study combines lab and animal testing to better understand how tilmicosin fights infections caused by Mycoplasma synoviae. This research helps optimize its use in poultry farming, improving animal health and minimizing the spread of resistant bacteria. Yan, Xiu, Jinxin Liu, Weihuo Li, Shuti Song, Zhaofeng Yao, Yixin Jia, Sheng Yuan, Hong Yang and Nan Zhang. 2024. “ The pharmacokinetics/pharmacodynamics integration of tilmicosin against Mycoplasma synoviae in vitro and in vivo.” Journal of Veterinary Pharmacology and Therapeutics 47: 503–511. https://doi.org/10.1111/jvp.13475 . Role of M-CSF and IL-34 in Canine Bone Cancer and Immune Response This research, led by Robinson et al. from Louisiana State University , looks at two molecules, M-CSF and IL-34, which play a role in regulating immune cells called macrophages. These molecules are studied in the context of canine osteosarcoma. The focus is on understanding the tumor immune microenvironment, which refers to the interactions between cancer cells and immune cells in and around the tumor. The researchers examined how M-CSF and IL-34 might influence macrophages in this environment, particularly how these molecules may help the tumor grow or evade immune defenses. By studying these immune-related molecules, the research aims to shed light on how osteosarcoma interacts with the immune system. This knowledge could lead to new treatments that target the tumor’s ability to manipulate the immune response, improving outcomes for dogs with osteosarcoma. Robinson, C.J., Moeller, C.E., Quick, C.N., Goodermuth, C.E., Carossino, M. and Withers, S.S. (2024), Macrophage Colony Stimulating Factor (M-CSF) and Interleukin-34 (IL-34) Expression in Canine Osteosarcoma in the Context of the Tumour Immune Microenvironment. Vet Comp Oncol, 22: 480-489. https://doi.org/10.1111/vco.12993 Diagnostics & Biomarkers Isolation of Tumor-Derived Particles from Dogs with Brain Tumors: A Pilot Study This study, by Simona Vincenti et al. from Universität Bern , Switzerland, focuses on understanding how cancer cells from intracranial tumors in dogs release tiny particles called extracellular vesicles (EVs) into the bloodstream. These EVs are small bits of the tumor that float around in the blood and can carry important
Thoughts on Veterinary Oncology
Thoughts on Veterinary Oncology Veterinary oncology is one of the fields that frankly intrigues me the most. While human medicine is experiencing a boom in treatment solutions, from ADC to bi-specific antibodies, from cell therapies to new small molecules, most of the veterinary treatments are restricted to surgery and radiation. Not surprisingly, two of these methods are the heroes of this week. What is surprising, is that while according to the WHO only 1 out of 5 humans will develop cancer over their 70-80 years lifespan, 1 out of 3 dogs and 1 out of 4 cats will develop cancer over their 10-15 years lifespan. That’s huge! All we can do, is just do out part to help develop new therapies and work together with the scientific community. Enjoy this week’s newsletter! Davide Confalonieri, PhD | CEO @Lab4Paws Clinical Effectiveness and Side Effects of Brief Palliative Radiation for Advanced Anal Gland Cancer in Dogs This study by Militi et al. from AniCura AOI Center AG, Hünenberg, Switzerland, examines how short cycles of palliative radiotherapy (pRT) can help manage advanced anal sac gland adenocarcinomas (AGASACA) in dogs. AGASACA often requires multiple treatments, especially in cases with severe symptoms. In this retrospective study, 12 dogs with advanced AGASACA received at least one short cycle of pRT (intensity-modulated radiotherapy, or IMRT, at 4 Gy twice daily over two days). Each dog was monitored from treatment until death, and their disease progression (PFS) and overall survival time (OST) were recorded. The study found that all dogs showed clinical improvement after receiving pRT, with the median progression-free survival at about 198 days and overall survival time around 250 days. Seven dogs experienced mild gastrointestinal side effects that resolved quickly, and no serious long-term effects were observed. Although the small sample size limited the ability to analyze additional treatments or prognostic factors, the results suggest that short cycles of pRT are a safe and effective option for providing symptom relief in dogs with advanced AGASACA. Militi, M., Botta, V., Heidrich, Y. et al. Efficacy and tolerance of short cycles of palliative radiotherapy in advanced anal sac adenocarcinomas in dogs. Vet. Oncol. 1, 9 (2024). https://doi.org/10.1186/s44356-024-00009-w Results and Surgical Risks of Removing Neck Tumors in Dogs: A 21-Case Study In this study, Kate Paskoff and colleagues from BluePearl Pet Hospital , California, USA, reviewed the outcomes and complications of surgery for carotid body paragangliomas, a rare tumor in dogs. The study included 21 dogs treated at nine specialty veterinary centers. Approximately half of the dogs (52%) experienced complications after surgery, such as airway obstruction, pneumonia, difficulty swallowing (megaesophagus), partial laryngeal paralysis, coughing, and Horner’s syndrome. Only one dog (4.7%) died shortly after surgery, showing a low perioperative mortality rate. The median survival time was 554 days, with 61% of dogs surviving at least one year and 42% surviving at least two years. This study, the largest of its kind, suggests that surgical removal of these tumors is generally safe and can provide extended survival for affected dogs. Paskoff, K., Matz, B., Fournier, Q., Aisa, J., Oblak, M., Bray, J. and Linden, D. (2024), Outcomes and Perioperative Complications of Surgical Resection on Canine Carotid Paragangliomas (21 Cases): A Veterinary Society of Surgical Oncology Study. Vet Comp Oncol. https://doi.org/10.1111/vco.13023 Impact of Tumor Grading on Survival in Dogs with Rib Cartilage Cancer In this study, Musset et al. from Iowa State University investigated whether the grade of rib chondrosarcoma, a type of bone cancer, affects survival in dogs. The team examined 22 cases and classified the tumors using a 3-tier grading system adapted from human medicine to see if higher grades were linked to shorter survival. The median survival time was about 1,427 days (ranging from 27 to 3,354 days), and no significant differences were found between grades in terms of survival outcomes. Other factors like age, weight, tumor location, appearance on X-rays, and additional treatments also did not significantly impact survival. Although grading did not predict outcomes in this small sample, further studies are needed to understand the role of tumor grade in canine rib chondrosarcoma prognosis. Musser, M., Meritet, D., Viall, A., Choi, E., Willcox, J. and Mathews, K. (2024), Prognostic Impact of a Histologic Grading Scheme in Dogs Diagnosed With Rib Chondrosarcoma. Vet Comp Oncol. https://doi.org/10.1111/vco.13025 Diagnostics & Biomarkers Comparing Three Blood Tests for Diagnosing Brucella suis in Dogs Using Advanced Statistical Methods In this study, Kneipp and colleagues from the University of Melbourne evaluated the effectiveness of three blood tests for diagnosing Brucella suis infection in dogs, an emerging zoonotic concern. The study tested 989 dog serum samples using the Rose Bengal test (RBRPT), complement fixation test (CFT), and a competitive ELISA (C-ELISA). A Bayesian analysis was used to account for overlap between tests. The RBRPT had the highest sensitivity, meaning it was best at identifying infected dogs, while the CFT was the most specific, meaning it was best at ruling out uninfected dogs. The C-ELISA showed strong overall performance. Combining the CFT and C-ELISA provided the best balance of sensitivity and specificity. All three tests had a high likelihood of correctly identifying dogs without B. suis infection, especially in low-prevalence settings. While each test is suitable for diagnosing B. suis in dogs, they work best when used together along with an evaluation of the dog’s risk factors and clinical history. Kneipp, C. C., Coilparampil, R., Westman, M., Suann, M., Robson, J., Firestone, S. M., Malik, R., Mor, S. M., Stevenson, M. A., & Wiethoelter, A. K. (2024). Evaluation of three serological tests for the diagnosis of Brucella suis in dogs using Bayesian latent class analysis. Preventive veterinary medicine, 233, 106345. Advance online publication. https://doi.org/10.1016/j.prevetmed.2024.106345 I am Davide – Founder & CEO of Lab4Paws Paws. With my life science company I help #AnimalHealth scientists develop therapeutic & diagnostic solutions for companion animals and work to reduce animal testing for human drug development. Like my content? Click my name + follow + 🔔
Autophagy and Cancer
Back to the lab, back to basic research: autophagy, ERK and Akt pathways are among some of the key topics of this week. The teams of Sakuma et al. and Vincente et al. studied these pathways in vitro and were able to give us great insights in the role of these pathways in cancer. Preclinical veterinary research lives from this: Bold ideas Empirical data In vitro work I am curious to see if any pharma will pick up these ideas and which new projects will be started because of these insights Enjoy this week’s edition! Davide Confalonieri, PhD | CEO @Lab4Paws In Vitro Effects of blocking cancer-related pathways in canine tumor cells In this study, Sakuma et al. from the Universität Tokio , Japan, investigated whether blocking two pathways—ERK and Akt, which are known to be active in CHS—could slow down CHS cell growth. The researchers tested drugs that specifically inhibit each pathway and observed their effects on CHS cell lines, both individually and in combination. The study found that ERK and Akt inhibitors successfully blocked their respective pathways in the cancer cells. However, while blocking the ERK pathway reduced cell growth, inhibiting the Akt pathway alone didn’t consistently prevent cell proliferation. They also tested two other drugs, dasatinib and trametinib, which target Akt and ERK pathways, respectively. Results showed that these drugs slowed down cell growth to varying degrees across different CHS cell lines. Interestingly, combining the drugs had a stronger effect in only some of the cell lines. This suggests that further research is needed to understand why certain CHS cells respond differently to these treatments. Sakuma, H., Tomiyasu, H., Tani, A., Goto-Koshino, Y., Tani, H., Ohno, K., Tsujimoto, H., Bonkobara, M., & Okuda, M. (2024). Antitumor effects of inhibitors of ERK and Akt pathways in canine histiocytic sarcoma cell lines. The Veterinary Journal, 106264. https://doi.org/10.1016/j.tvjl.2024.106264 Cell recycling markers in dog skin tumors: A microscopic study This study by Vicente et al. from the University of Bologna (Alma Mater Studiorum – Università di Bologna) , Italy, examined the role of autophagy in canine mast cell tumors (MCTs) by analyzing the expression of two key proteins, Beclin-1 and LC3B, which are involved in the autophagy process. Autophagy, a cellular process that helps remove damaged components, is believed to impact cancer cell survival and tumor progression. Using immunohistochemical and immuno-ultrastructural techniques, the researchers studied the levels of Beclin-1 and LC3B in MCT samples. Their findings revealed varying levels of these proteins, suggesting differences in autophagic activity among tumors. This variation could help explain why some mast cell tumors are more aggressive or respond differently to treatment. In summary, this research highlights the potential role of autophagy in MCT progression and suggests that Beclin-1 and LC3B expression might be useful markers for understanding tumor behavior and possibly guiding treatment decisions in canine MCTs. Vicente, G. P., Della Salda, L., & Strefezzi, R. F. (2024). Beclin-1 and LC3B expression in canine mast cell tumours: an immuno-ultrastructural and immunohistochemical study of autophagy. Veterinary Quarterly, 44(1), 1–15. https://doi.org/10.1080/01652176.2024.2419585 Diagnostics & Biomarkers Urine protein signals kidney damage in cats This study by Chen et al. from the The Hebrew University of Jerusalem , Israel,explored the potential of urinary Cystatin B as an indicator of acute kidney injury (AKI) in cats. AKI is challenging to detect early in cats, making timely diagnosis crucial. Cystatin B, a protein found in urine, was evaluated for its reliability as a marker for AKI. The researchers measured Cystatin B levels in cats with and without AKI to determine if elevated levels correlated with kidney injury. Their findings suggest that urinary Cystatin B could serve as an early and specific marker for AKI in cats, potentially helping veterinarians diagnose and manage kidney issues sooner. This promising marker could improve outcomes for cats by enabling faster intervention. Chen, H., Avital, Y., Peterson, S., Ouyang, Z., Yerramilli, M., Aroch, I., & Segev, G. (2024). Urinary Cystatin B as a marker of acute kidney injury in cats. The Veterinary Journal, 106262. https://doi.org/10.1016/j.tvjl.2024.106262 Heart and kidney hormone levels in healthy small dogs This study by Galizzi et al. from the Università degli Studi di Milano , Italy, aimed to establish reference ranges for two potential biomarkers—N-terminal pro-B-type natriuretic peptide (NT-proBNP) and urinary aldosterone-to-creatinine ratio (UAldo: C)—specifically in healthy Chihuahuas, as these markers differ across breeds. Forty-three healthy Chihuahuas were tested. The median NT-proBNP was 347 pmol/L, and the median UAldo: C was 2.59 µg/g. Most Chihuahuas (91%) fell below the general threshold for NT-proBNP (900 pmol/L), suggesting that NT-proBNP might have breed-specific cut-offs. The UAldo: C values were generally higher than in other breeds, supporting the idea that Chihuahuas may have distinct renin-angiotensin-aldosterone system activity. No significant differences were found between males and females for either marker. In summary, these findings provide breed-specific reference intervals for NT-proBNP and UAldo: C in Chihuahuas, which could improve heart disease screening and management for this breed. Galizzi, A., Dossi, G., Pocar, P. et al. Plasma N-terminal pro-B-type natriuretic peptide and urinary aldosterone-to-creatinine ratio in healthy Chihuahuas. BMC Vet Res 20, 501 (2024). https://doi.org/10.1186/s12917-024-04344-w Effects of sildenafil on kidney health in cats with worsening chronic kidney disease This study by Maden et al. from the University of Ankara, Türkyie, explored the effects of sildenafil on mitochondrial health and kidney damage in cats with acute on chronic kidney disease (ACKD). Sildenafil is known for activating the cGMP/NO pathway, which could support kidney function and reduce damage in cases of kidney disease. Thirty-three cats were involved, divided into healthy (non-azotemic) and ACKD groups. Both groups received sildenafil for 30 days. Researchers measured various kidney-related biomarkers in their blood and urine over this period. Results showed that sildenafil raised cGMP levels in healthy cats but had limited impact in the ACKD cats. Some markers of kidney function (such as NO) increased in the ACKD cats, indicating some benefit in glomerular filtration. However, the drug did not significantly reduce kidney damage or fibrosis linked to the TGF-β/SMAD pathway. In summary, sildenafil showed
EV and Biomarkers
Comparative biology is big in veterinary science It helps us understand, it helps us develop new solutions So that, when we see studies on Extracellular Vescicles and CDB, we have to smile real big. Because it means change is coming, and even the newst things in human research are coming to veterinary science. This week’s big shoutout goes to Thierry Olivry and his team at Nextmune for their new Multiplex Molecular Macroarray and to Tania Gutiérrez Riquelme and colleagues for their great proteomics work on EV! Enjoy this week’s edition! Davide Confalonieri, PhD | CEO @Lab4Paws In Vitro Investigation on the In Vitro Effects of Resveratrol on Peripheral Blood Mononuclear Cells Harvested from Healthy and Atopic Dogs In this study Domenico Santoro from the University of Florida, USA, evaluates resveratrol’s potential as a safer anti-inflammatory treatment for canine atopic dermatitis (AD) compared to conventional therapies, which often have side effects and high costs. The in vitro effects of resveratrol were examined on peripheral blood mononuclear cells (PBMCs) from nine healthy and 11 atopic dogs. PBMCs were exposed to resveratrol at various concentrations (1.5–9 μg/mL), with and without phytohemagglutinin stimulation. Cytotoxicity, host defense peptides (HDPs), oxidative stress markers (catalase and superoxide dismutase), and pro-inflammatory cytokines were assessed after 24 hours. Results indicated no cytotoxicity in either group across all conditions. Low concentrations of resveratrol increased catalase levels only in healthy PBMCs, but HDP levels remained unaffected. Significant reductions in monocyte chemotactic protein-1 and interleukin-6 were observed at the highest concentration (9 μg/mL) in both unstimulated healthy and stimulated atopic PBMCs. Overall, resveratrol demonstrated minimal effects on HDP secretion and pro-inflammatory cytokine levels at the tested concentrations, while proving non-toxic to PBMCs from both healthy and atopic dogs. Santoro D, Nadeau P., Archer L..Investigation on the in vitro effects of resveratrol on peripheral blood mononuclear cells harvested from healthy and atopic dogs. Research in Veterinary Science. 2024, 105441, ISSN 0034-5288, https://doi.org/10.1016/j.rvsc.2024.105441. Proteomic Analysis of Extracellular Vesicles Derived from Canine Mammary Tumour Cell Lines Identifies Protein Signatures Specific for Disease State This study from Tania Gutiérrez Riquelme, from the Freie Universität Berlin, Germany, explores the proteomic profiles of extracellular vesicles (EVs) derived from canine mammary tumour (CMT) cell lines to identify non-invasive diagnostic markers for CMT. EVs, containing unique protein and RNA cargo, were isolated from five distinct canine mammary cell lines representing non-neoplastic, adenoma, and carcinoma states. Whole-cell lysates (WCLs) and EV lysates underwent LC-MS/MS analysis, with protein abundance compared between groups. Distinct protein signatures were observed in WCLs and EVs, particularly for proteins related to cell adhesion, migration, and RNA processing. Weighted gene correlation network analysis (WGCNA) identified co-abundant EV protein clusters specific to CMT stages, revealing distinct adenoma and carcinoma EV signatures, absent in WCLs. Key proteins like biglycan emerged as potential biomarkers for canine mammary carcinomas, offering a foundation for developing a liquid biopsy approach for CMT diagnosis, minimizing the need for invasive tissue biopsies. Gutierrez-Riquelme, T., Karkossa, I., Schubert, K. et al. Proteomic analysis of extracellular vesicles derived from canine mammary tumour cell lines identifies protein signatures specific for disease state. BMC Vet Res 20, 488 (2024). https://doi.org/10.1186/s12917-024-04331-1 In Vitro Antitumor Effect of Oils Rich in CBD and THC Cannabis Extract in Canine Prostate Carcinoma Cell Lines Calheiros et al, Sao Paulo State University- The Universidade Estadual Paulista (UNESP), Brazil, investigates the antitumor potential of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in canine prostate carcinoma cell lines, PC1 and PC2. Prostate cancer in dogs presents similarities to androgen-independent prostate cancer in humans, making it a valuable model for comparative research. Results demonstrated that both CBD- and THC-rich cannabis extracts significantly inhibited cell proliferation, with half-maximal inhibitory concentrations (IC50) at 3.43 and 3.57 μM for CBD and 4.90 and 4.48 μM for THC. Furthermore, cell death was confirmed via Annexin V and Propidium iodide staining. These findings suggest a promising direction for further research on the therapeutic applications of cannabis extracts in treating canine prostate carcinoma, with potential implications for human medicine. Calheiros, L.G.R.d.M.; Pedro, G.; Oliveira da Silva, T.; Amorim, R.M.; Alves, C.E.F.; Laufer-Amorim, R. In Vitro Antitumor Effect of Oils Rich in CBD and THC Cannabis Extract in Canine Prostate Carcinoma Cell Lines. Vet. Sci. 2024, 11, 501. https://doi.org/10.3390/vetsci11100501 Diagnostics & Biomarkers Validation of a Multiplex Molecular Macroarray for the Determination of Allergen-Specific IgE Sensitizations in Dogs Thierry Olivry and his team at Nextmune, Sweden, validated the Pet Allergy Xplorer (PAX), a novel multiplex molecular macroarray designed to detect IgE sensitizations in dogs. Developed by Nextmune, this platform incorporates both allergen extracts and molecular components to provide detailed insights into allergen cross-reactivity. The validation process included testing the specificity and accuracy of IgE detection, as well as evaluating confounding factors such as hemolysis and lipemia. Notably, the PAX includes a cross-reactive carbohydrate determinants (CCD) detection and blocking feature, increasing result reliability. Data from over 23,000 European dogs revealed sensitization rates across 145 environmental and insect allergens, showcasing PAX as an effective, reproducible tool for diagnosing canine allergies. Olivry, T.; Fontao, A.M.; Aumayr, M.; Ivanovova, N.P.; Mitterer, G.; Harwanegg, C. Validation of a Multiplex Molecular Macroarray for the Determination of Allergen-Specific IgE Sensitizations in Dogs. Vet. Sci. 2024, 11, 482. https://doi.org/10.3390/vetsci11100482 Immunohistochemical Expression of Tenascin-C in Canine Meningiomas This study from Sant’Ana et al, Universidade de Brasília, Brazil, investigated the expression of tenascin-C (TN-C), a marker associated with more aggressive central nervous system tumors in humans, within different grades of canine meningiomas. The study analyzed 21 cases of canine meningiomas classified as grade I (12 cases), grade II (6 cases), and grade III (3 cases). Immunohistochemistry for TN-C, along with epithelial membrane antigen (EMA), Ki-67, pan-cytokeratin (Pan CK), and vimentin, was performed to characterize TN-C distribution. Results showed increased TN-C immunoreactivity corresponding with tumor grade, from mild in grade I to moderate in grade II, and moderate to severe in grade III. TN-C positivity was primarily noted in the tumor stroma and perivascular spaces, particularly in higher-grade tumors. The findings suggest that TN-C may serve as a valuable
